PROJECT SUMMARY The objective of this proposal is to enhance the capability of investigators at Northwestern University to investigate the electrophysiological, contractile, and pharmacological properties of cultured cardiomyocytes. This objective will be achieved by the purchase and installation of a CardioExcyte 96 system manufactured by Nanion Technologies. The system is a screening platform enabling reliable, label-free measurements of short- and long-term compound effects for drug safety screening, contractility assays, and functional investigations of electrical activity of cultured cardiomyocytes. This hybrid instrument combines measurement of cell monolayer impedance, which correlates with cell contractility, with extracellular field potential (EFP) recordings generated by cellular action potentials. The CardioExcyte 96 is a fully automated device, recording from 96 wells at a time. The system will be configured with an incubation system to maintain physiological temperature, automated pipetting station for reproducible cell seeding and compound handling, and a 96-well optical stimulation module for noninvasive optogenetic pacing of cardiomyocytes. A powerful and user-friendly software drives operation of the instrument, performs data acquisition and analysis. The instrument will be immediately used by a diverse group of biomedical scientists who use cultured human and rodent cardiomyocytes to study a diverse array of heart diseases, and who need to test lead compounds for human cardiomyocyte toxicity as part of drug development programs. The CardioExcyte 96 will be managed by the Northwestern University High Throughput Analysis Laboratory (NU-HTA), which supports a range of technologies enabling high throughput screening for drug discovery and biology. Although NU-HTA will oversee management of the instrument, the CardioExcyte 96 will physically reside initially within space provided by the Department of Pharmacology, which will facilitate ready access to most Major and Minor users named in this application. The placement of the instrument in Pharmacology is part of an ongoing collaboration with NU-HTA that seeks to expand services on the Chicago campus of Northwestern University. Strong institutional support for the instrument and its deployment will be provided, and effective oversight will be achieved by an internal advisory committee. The instrument is expected to enhance the success of several NIH-funded research projects and provide a new platform for active and future research in drug screening, cell toxicity research, and physiological investigations using cardiomyocytes.